PMID- 10487661
OWN - NLM
STAT- MEDLINE
DCOM- 19991006
LR  - 20131121
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 84
IP  - 9
DP  - 1999 Sep
TI  - Autosomal dominant hypoparathyroidism associated with short stature and premature
      osteoarthritis.
PG  - 3036-40
AB  - Familial hypoparathyroidism is an unusual and genetically heterogeneous group of 
      disorders that may be isolated or may be associated with congenital or acquired
      abnormalities in other organs or glands. We have evaluated a family with a novel 
      syndrome of autosomal dominant hypoparathyroidism, short stature, and premature
      osteoarthritis. A 74-yr-old female (generation I) presented with
      hypoparathyroidism, a movement disorder secondary to ectopic calcification of the
      cerebellum and basal ganglia, and a history of knee and hip replacements for
      osteoarthritis. Two members of generation II and one member of generation III
      were also documented with hypoparathyroidism, short stature, and premature
      osteoarthritis evident as early as 11 yr. Because of the known association
      between autosomal dominant hypoparathyroidism and activating mutations of the
      calcium-sensing receptor (CaR) gene, further studies were performed. Sequencing
      of PCR-amplified genomic DNA revealed a leucine to valine substitution at
      position 616 in the first transmembrane domain of the CaR, which cosegregated
      with the disorder. However, this amino acid sequence change did not affect the
      total accumulation of inositol phosphates as a function of extracellular calcium 
      concentrations in transfected HEK-293 cells. In conclusion, a sequence alteration
      in the coding region of the CaR gene was identified, but is not conclusively
      involved in the etiology of this novel syndrome. The cosegregation of
      hypoparathyroidism, short stature, and osteoarthritis in this kindred does
      suggest a genetic abnormality involving a common molecular mechanism in
      parathyroid, bone, and cartilage.
FAU - Stock, J L
AU  - Stock JL
AD  - Division of Endocrinology, University of Massachusetts Memorial Health Care and
      University of Massachusetts Medical School, Worcester 01605, USA.
      jlstock@lilly.com
FAU - Brown, R S
AU  - Brown RS
FAU - Baron, J
AU  - Baron J
FAU - Coderre, J A
AU  - Coderre JA
FAU - Mancilla, E
AU  - Mancilla E
FAU - De Luca, F
AU  - De Luca F
FAU - Ray, K
AU  - Ray K
FAU - Mericq, M V
AU  - Mericq MV
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Calcium-Binding Proteins)
RN  - EC 3.1.21.- (endodeoxyribonuclease MaeIII)
RN  - EC 3.1.21.4 (Deoxyribonucleases, Type II Site-Specific)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Body Height/*genetics
MH  - Calcium/blood
MH  - Calcium-Binding Proteins/*genetics
MH  - Child
MH  - DNA Mutational Analysis
MH  - Deoxyribonucleases, Type II Site-Specific/metabolism
MH  - Female
MH  - Humans
MH  - Hypoparathyroidism/*genetics
MH  - Male
MH  - Middle Aged
MH  - Osteoarthritis/*genetics
MH  - Pedigree
MH  - Polymerase Chain Reaction
MH  - Sequence Analysis, DNA
MH  - Transfection
EDAT- 1999/09/16 00:00
MHDA- 1999/09/16 00:01
CRDT- 1999/09/16 00:00
PHST- 1999/09/16 00:00 [pubmed]
PHST- 1999/09/16 00:01 [medline]
PHST- 1999/09/16 00:00 [entrez]
AID - 10.1210/jcem.84.9.5977 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1999 Sep;84(9):3036-40. doi: 10.1210/jcem.84.9.5977.